26512
Multisite Randomised Controlled Trial of Fluoxetine Versus Placebo for the Treatment of Restricted Repetitive and Stereotyped Behaviours in Children and Adolescents with Autism
Two Cochrane reviews of the use of SSRIs in autism have been published, the last one in 2013. Fluoxetine has only been studied in clinical trials with small numbers of children. As this is a commonly prescribed SSRI in Australia, this trial was important to undertake. The only SSRI to be studied with sufficient power to answer the question about safety and efficacy is citalopram.
Objectives: Maladaptive repetitive activities, stereotypies and inflexibility have an impact on children's participation and function in their daily life. An adequately powered randomized double blind placebo controlled trial to establish whether there is a reduction in these troublesome behaviours was commenced in 2010. Low dose fluoxetine was compared to placebo.
Other aims of the study included frequency and type of adverse events and exploration of whether there is a relationship between the individual’s serotonin transporter genotype and response to treatment.
Methods: Patients aged 7 years 6 months to 17 years with a diagnosis of autism spectrum disorder were recruited in three states of Australia. We included children on stimulant medication for co-morbid attention deficit hyperactivity disorder. Exclusion criteria included being on any other psychotropic medications within 6 weeks prior to study entry, alternative therapies such as St John's Wort or co-morbid significant medical conditions such as cardiac, liver or kidney disease or uncontrolled epilepsy.
Detailed medical history and physical examination, an ADI-R and a number of rating scales were administered. Eligible participants were randomized to either placebo or active fluoxetine groups with medication being titrated upwards over a four-week period. Responses to medication were monitored on a weekly/fortnightly basis using the Clinical Global Impressions Scale (CGI). The primary outcome measure was the Children’s Yale-Brown Obsessive Compulsive Scale- Modified for Pervasive Developmental Disorders (CYBOCS-PDD) at 16 weeks. Secondary outcome measures included the Aberrant Behaviour Scale (ABC), Spence Children’s Anxiety Scale Parent version (SCAS-P) and the Repetitive Behaviours Scale (RBS-R) also at 16 weeks. Participants were also invited to undergo genetic testing for SLC6A4 allele variants via a cheek swab.
The primary outcome (total score on the CYBOCS-PDD at 16 weeks) will be compared for the active and placebo groups using unadjusted linear regression. Secondary outcomes will also be compared using unadjusted linear regression with proportions compared using unadjusted logistic regression.
Results: 146 patients were recruited to the study over a 7 year period. Our statistical analysis is currently being completed and will be available soon.
Conclusions: This trial has sufficient power to finally answer the question about whether the use of fluoxetine is safe and effective for troublesome symptoms in children and adolescents with autism spectrum disorder.